scs-analysis: Tools for Single Cell Genomics

Documented in as.CellDataSet.Seurat as.Seurat.CellDataSet as.Seurat.SingleCellExperiment as.SingleCellExperiment.Seurat as.sparse.H5Group CellsByImage Cells.SCTModel Cells.SlideSeq Cells.STARmap Cells.VisiumV1 CreateSCTAssayObject DietSeurat FilterSlideSeq GetAssay.Seurat GetImage.SlideSeq GetImage.STARmap GetImage.VisiumV1 GetIntegrationData GetTissueCoordinates.SlideSeq GetTissueCoordinates.STARmap GetTissueCoordinates.VisiumV1 levels.SCTAssay merge.SCTAssay Radius.SlideSeq Radius.STARmap Radius.VisiumV1 RenameCells.SCTAssay RenameCells.SlideSeq RenameCells.STARmap RenameCells.VisiumV1 scalefactors ScaleFactors.VisiumV1 SCTResults.SCTAssay SCTResults.SCTModel SCTResults.Seurat SetIntegrationData SplitObject subset.AnchorSet TopCells TopFeatures TopNeighbors UpdateSCTAssays

#' @include reexports.R
#' @include generics.R
#' @importFrom Rcpp evalCpp
#' @importFrom Matrix colSums rowSums colMeans rowMeans
#' @importFrom methods setClass setOldClass setClassUnion slot
#' slot<- setMethod new signature slotNames is setAs setValidity .hasSlot
#' @importClassesFrom Matrix dgCMatrix
#' @useDynLib Seurat
#'
NULL

#%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%
# Class definitions
#%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%

setOldClass(Classes = 'package_version')

#' The AnchorSet Class
#'
#' The AnchorSet class is an intermediate data storage class that stores the anchors and other
#' related information needed for performing downstream analyses - namely data integration
#' (\code{\link{IntegrateData}}) and data transfer (\code{\link{TransferData}}).
#'
#' @slot object.list List of objects used to create anchors
#' @slot reference.cells List of cell names in the reference dataset - needed when performing data
#' transfer.
#' @slot reference.objects Position of reference object/s in object.list
#' @slot query.cells List of cell names in the query dataset - needed when performing data transfer
#' @slot anchors The anchor matrix. This contains the cell indices of both anchor pair cells, the
#' anchor score, and the index of the original dataset in the object.list for cell1 and cell2 of
#' the anchor.
#' @slot offsets The offsets used to enable cell look up in downstream functions
#' @slot anchor.features The features used when performing anchor finding.
#' @slot neighbors List containing Neighbor objects for reuse later (e.g. mapping)
#' @slot command Store log of parameters that were used
#'
#' @name AnchorSet-class
#' @rdname AnchorSet-class
#' @concept objects
#' @exportClass AnchorSet
#'
AnchorSet <- setClass(
  Class = "AnchorSet",
  contains = 'VIRTUAL',
  slots = list(
    object.list = "list",
    reference.cells = "vector",
    reference.objects = "vector",
    query.cells = "vector",
    anchors = "ANY",
    offsets = "ANY",
    anchor.features = "ANY",
    neighbors = "list",
    command = "ANY"
  )
)

#' The TransferAnchorSet Class
#'
#' Inherits from the Anchorset class. Implemented mainly for method dispatch
#' purposes.  See \code{\link{AnchorSet}} for slot details.
#'
#' @name TransferAnchorSet-class
#' @rdname TransferAnchorSet-class
#' @concept objects
#' @exportClass TransferAnchorSet
#'
TransferAnchorSet <- setClass(
  Class = "TransferAnchorSet",
  contains = "AnchorSet"
)

#' The IntegrationAnchorSet Class
#'
#' Inherits from the Anchorset class. Implemented mainly for method dispatch
#' purposes.  See \code{\link{AnchorSet}} for slot details.
#'
#' @name IntegrationAnchorSet-class
#' @rdname IntegrationAnchorSet-class
#' @concept objects
#' @exportClass IntegrationAnchorSet
#'
IntegrationAnchorSet <- setClass(
  Class = "IntegrationAnchorSet",
  contains = "AnchorSet"
)

#' The ModalityWeights Class
#'
#' The ModalityWeights class is an intermediate data storage class that stores the modality weight and other
#' related information needed for performing downstream analyses - namely data integration
#' (\code{FindModalityWeights}) and data transfer (\code{\link{FindMultiModalNeighbors}}).
#'
#' @slot modality.weight.list A list of modality weights value from all modalities
#' @slot modality.assay Names of assays for the list of dimensional reductions
#' @slot params A list of parameters used in the FindModalityWeights
#' @slot score.matrix a list of score matrices representing cross and within-modality prediction
#' score, and kernel value
#' @slot command Store log of parameters that were used
#'
#' @name ModalityWeights-class
#' @rdname ModalityWeights-class
#' @concept objects
#' @exportClass ModalityWeights
#'
ModalityWeights <- setClass(
  Class = "ModalityWeights",
  slots = list(
    modality.weight.list = "list",
    modality.assay = "vector",
    params = "list",
    score.matrix = "list",
    command = "ANY"
  )
)

#' The IntegrationData Class
#'
#' The IntegrationData object is an intermediate storage container used internally throughout the
#' integration procedure to hold bits of data that are useful downstream.
#'
#' @slot neighbors List of neighborhood information for cells (outputs of \code{RANN::nn2})
#' @slot weights Anchor weight matrix
#' @slot integration.matrix Integration matrix
#' @slot anchors Anchor matrix
#' @slot offsets The offsets used to enable cell look up in downstream functions
#' @slot objects.ncell Number of cells in each object in the object.list
#' @slot sample.tree Sample tree used for ordering multi-dataset integration
#'
#' @name IntegrationData-class
#' @rdname IntegrationData-class
#' @concept objects
#' @exportClass IntegrationData
#'
IntegrationData <- setClass(
  Class = "IntegrationData",
  slots = list(
    neighbors = "ANY",
    weights = "ANY",
    integration.matrix = "ANY",
    anchors = "ANY",
    offsets = "ANY",
    objects.ncell = "ANY",
    sample.tree = "ANY"
  )
)

#' The SCTModel Class
#'
#' The SCTModel object is a model and parameters storage from SCTransform.
#' It can be used to calculate Pearson residuals for new genes.
#'
#' @slot feature.attributes A data.frame with feature attributes in SCTransform
#' @slot cell.attributes A data.frame with cell attributes in SCTransform
#' @slot clips A list of two numeric of length two specifying the min and max
#' values the Pearson residual will be clipped to. One for vst and one for
#' SCTransform
#' @slot umi.assay Name of the assay of the seurat object containing UMI matrix
#' and the default is RNA
#' @slot model A formula used in SCTransform
#' @slot arguments other information used in SCTransform
#'
#' @seealso \code{\link{Assay}}
#'
#' @name SCTAssay-class
#' @rdname SCTAssay-class
#'
#' @examples
#' \dontrun{
#' # SCTAssay objects are generated from SCTransform
#' pbmc_small <- SCTransform(pbmc_small)
#' }
#'
SCTModel <- setClass(
  Class = 'SCTModel',
  slots = c(
    feature.attributes = 'data.frame',
    cell.attributes = 'data.frame',
    clips = 'list',
    umi.assay = 'character',
    model = 'character',
    arguments = "list"
  )
)

#' The SCTAssay Class
#'
#' The SCTAssay object contains all the information found in an \code{\link{Assay}}
#' object, with extra information from the results of \code{\link{SCTransform}}
#'
#' @slot SCTModel.list A list containing SCT models
#'
#' @seealso \code{\link{Assay}}
#'
#' @name SCTAssay-class
#' @rdname SCTAssay-class
#'
#' @examples
#' # SCTAssay objects are generated from SCTransform
#' pbmc_small <- SCTransform(pbmc_small)
#' pbmc_small[["SCT"]]
#'
SCTAssay <- setClass(
  Class = 'SCTAssay',
  contains = 'Assay',
  slots = c(
    SCTModel.list = 'list'
  )
)


#' @note \code{scalefactors} objects can be created with \code{scalefactors()}
#'
#' @param spot Spot full resolution scale factor
#' @param fiducial Fiducial full resolution scale factor
#' @param hires High resolutoin scale factor
#' @param lowres Low resolution scale factor
#'
#' @rdname ScaleFactors
#' @concept objects
#' @export
#'
scalefactors <- function(spot, fiducial, hires, lowres) {
  object <- list(
    spot = spot,
    fiducial = fiducial,
    hires = hires,
    lowres = lowres
  )
  object <- sapply(X = object, FUN = as.numeric, simplify = FALSE, USE.NAMES = TRUE)
  return(structure(.Data = object, class = 'scalefactors'))
}

setOldClass(Classes = c('scalefactors'))

#' The SlideSeq class
#'
#' The SlideSeq class represents spatial information from the Slide-seq platform
#'
#' @inheritSection SeuratObject::SpatialImage Slots
#' @slot coordinates ...
#' @slot ...
#'
SlideSeq <- setClass(
  Class = 'SlideSeq',
  contains = 'SpatialImage',
  slots = list(
    'coordinates' = 'data.frame'
  )
)

#' The STARmap class
#'
#'
#' @inheritSection SeuratObject::SpatialImage Slots
#' @slot ...
#'
STARmap <- setClass(
  Class = 'STARmap',
  contains = 'SpatialImage',
  slots = list(
    'coordinates' = 'data.frame',
    'qhulls' = 'data.frame'
  )
)

#' The VisiumV1 class
#'
#' The VisiumV1 class represents spatial information from the 10X Genomics Visium
#' platform
#'
#' @slot image A three-dimensional array with PNG image data, see
#' \code{\link[png]{readPNG}} for more details
#' @slot scale.factors An object of class \code{\link{scalefactors}}; see
#' \code{\link{scalefactors}} for more information
#' @slot coordinates A data frame with tissue coordinate information
#' @slot spot.radius Single numeric value giving the radius of the spots
#'
#' @name VisiumV1-class
#' @rdname VisiumV1-class
#' @concept objects
#' @exportClass VisiumV1
#'
VisiumV1 <- setClass(
  Class = 'VisiumV1',
  contains = 'SpatialImage',
  slots = list(
    'image' = 'array',
    'scale.factors' = 'scalefactors',
    'coordinates' = 'data.frame',
    'spot.radius' = 'numeric'
  )
)

setClass(Class = 'SliceImage', contains = 'VisiumV1')

#%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%
# Functions
#%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%

#' Get a vector of cell names associated with an image (or set of images)
#'
#' @param object Seurat object
#' @param images Vector of image names
#' @param unlist Return as a single vector of cell names as opposed to a list,
#' named by image name.
#'
#' @return A vector of cell names
#' @concept objects
#'
#' @examples
#' \dontrun{
#' CellsByImage(object = object, images = "slice1")
#' }
#'
CellsByImage <- function(object, images = NULL, unlist = FALSE) {
  images <- images %||% Images(object = object)
  cells <- sapply(
    X = images,
    FUN = function(x) {
      Cells(x = object[[x]])
    },
    simplify = FALSE,
    USE.NAMES = TRUE
  )
  if (unlist) {
    cells <- unname(obj = unlist(x = cells))
  }
  return(cells)
}

#' Create a SCT Assay object
#'
#' Create a SCT object from a feature (e.g. gene) expression matrix and a list of SCTModels.
#' The expected format of the input matrix is features x cells.
#'
#' Non-unique cell or feature names are not allowed. Please make unique before
#' calling this function.
#' @param scale.data a residual matrix
#' @param SCTModel.list list of SCTModels
#' @param umi.assay The UMI assay name. Default is RNA
#' @inheritParams SeuratObject::CreateAssayObject
#'
#' @importFrom methods as
#' @importFrom Matrix colSums rowSums
#'
#' @export
#'
#'
CreateSCTAssayObject <- function(
  counts,
  data,
  scale.data = NULL,
  umi.assay = "RNA",
  min.cells = 0,
  min.features = 0,
  SCTModel.list = NULL
) {
  assay <- CreateAssayObject(
    counts = counts,
    data = data,
    min.cells = min.cells,
    min.features = min.features
  )
  if (!is.null(scale.data)) {
    assay <- SetAssayData(object = assay, slot = "scale.data", new.data = scale.data)
  }

  slot(object = assay, name = "assay.orig") <- umi.assay

  #checking SCTModel.list format
  if (is.null(x = SCTModel.list)) {
    SCTModel.type <- "none"
    warning("An empty SCTModel will be generated due to no SCTModel input")
  } else {
    if (inherits(x = SCTModel.list, what = "SCTModel")) {
      SCTModel.list <- list(model1 = SCTModel.list)
      SCTModel.type <- "SCTModel.list"
    } else if (inherits(x = SCTModel.list, what = "list")) {
      if (inherits(x = SCTModel.list[[1]], what = "SCTModel")){
        SCTModel.type <-  "SCTModel.list"
      } else if (IsVSTout(vst.out = SCTModel.list)){
        SCTModel.type <- "vst.out"
      } else if (IsVSTout(SCTModel.list[[1]])) {
        SCTModel.type <- "vst.set"
      } else {
        stop("SCTModel input is not a correct format")
      }
    }
  }
  model.list <- switch(
    EXPR = SCTModel.type,
    "none" = {
      list()
    },
    "SCTModel.list" = {
      SCTModel.list <- lapply(X = SCTModel.list, FUN = function(model) {
        select.cell <- intersect(x = Cells(x = model), Cells(x = assay))
        if (length(x = select.cell) == 0) {
          stop("Cells in SCTModel.list don't match Cells in assay")
        } else {
          model@cell.attributes <- model@cell.attributes[select.cell, , drop = FALSE]
        }
        return(model)
      })
      SCTModel.list
    },
    "vst.out" = {
      SCTModel.list$umi.assay <- umi.assay
      SCTModel.list <- PrepVSTResults(
        vst.res = SCTModel.list,
        cell.names = Cells(x = assay)
      )
      list(model1 = SCTModel.list)
    },
    "vst.set" = {
      new.model <- lapply(
        X = SCTModel.list,
        FUN = function(vst.res) {
          vst.res$umi.assay <- umi.assay
          return(PrepVSTResults(vst.res = vst.res, cell.names = colnames(x = assay)))
        }
      )
      names(x = new.model) <- paste0("model", 1:length(x = new.model))
      new.model
    }
  )
  assay <- new(
    Class = "SCTAssay",
    assay,
    SCTModel.list = model.list
  )
  return(assay)
}

#' Slim down a Seurat object
#'
#' Keep only certain aspects of the Seurat object. Can be useful in functions that utilize merge as
#' it reduces the amount of data in the merge.
#'
#' @param object Seurat object
#' @param counts Preserve the count matrices for the assays specified
#' @param data Preserve the data slot for the assays specified
#' @param scale.data Preserve the scale.data slot for the assays specified
#' @param features Only keep a subset of features, defaults to all features
#' @param assays Only keep a subset of assays specified here
#' @param dimreducs Only keep a subset of DimReducs specified here (if NULL,
#' remove all DimReducs)
#' @param graphs Only keep a subset of Graphs specified here (if NULL, remove
#' all Graphs)
#'
#' @export
#' @concept objects
#'
DietSeurat <- function(
  object,
  counts = TRUE,
  data = TRUE,
  scale.data = FALSE,
  features = NULL,
  assays = NULL,
  dimreducs = NULL,
  graphs = NULL
) {
  object <- UpdateSlots(object = object)
  assays <- assays %||% FilterObjects(object = object, classes.keep = "Assay")
  assays <- assays[assays %in% FilterObjects(object = object, classes.keep = 'Assay')]
  if (length(x = assays) == 0) {
    stop("No assays provided were found in the Seurat object")
  }
  if (!DefaultAssay(object = object) %in% assays) {
    stop("The default assay is slated to be removed, please change the default assay")
  }
  if (!counts && !data) {
    stop("Either one or both of 'counts' and 'data' must be kept")
  }
  for (assay in FilterObjects(object = object, classes.keep = 'Assay')) {
    if (!(assay %in% assays)) {
      object[[assay]] <- NULL
    } else {
      if (!is.null(x = features)) {
        features.assay <- intersect(x = features, y = rownames(x = object[[assay]]))
        if (length(x = features.assay) == 0) {
          if (assay == DefaultAssay(object = object)) {
            stop("The default assay is slated to be removed, please change the default assay")
          } else {
            warning("No features found in assay '", assay, "', removing...")
            object[[assay]] <- NULL
          }
        } else {
          object[[assay]] <- subset(x = object[[assay]], features = features.assay)
        }
      }
      if (!counts) {
        slot(object = object[[assay]], name = 'counts') <- new(Class = 'matrix')
      }
      if (!data) {
        stop('data = FALSE currently not supported')
      }
      if (!scale.data) {
        slot(object = object[[assay]], name = 'scale.data') <- new(Class = 'matrix')
      }
    }
  }
  # remove unspecified DimReducs and Graphs
  all.objects <- FilterObjects(object = object, classes.keep = c('DimReduc', 'Graph'))
  objects.to.remove <- all.objects[!all.objects %in% c(dimreducs, graphs)]
  for (ob in objects.to.remove) {
    object[[ob]] <- NULL
  }
  return(object)
}

#' Filter stray beads from Slide-seq puck
#'
#' This function is useful for removing stray beads that fall outside the main
#' Slide-seq puck area. Essentially, it's a circular filter where you set a
#' center and radius defining a circle of beads to keep. If the center is not
#' set, it will be estimated from the bead coordinates (removing the 1st and
#' 99th quantile to avoid skewing the center by the stray beads). By default,
#' this function will display a \code{\link{SpatialDimPlot}} showing which cells
#' were removed for easy adjustment of the center and/or radius.
#'
#' @param object Seurat object with slide-seq data
#' @param image Name of the image where the coordinates are stored
#' @param center Vector specifying the x and y coordinates for the center of the
#' inclusion circle
#' @param radius Radius of the circle of inclusion
#' @param do.plot Display a \code{\link{SpatialDimPlot}} with the cells being
#' removed labeled.
#'
#' @return Returns a Seurat object with only the subset of cells that pass the
#' circular filter
#'
#' @concept objects
#' @examples
#' \dontrun{
#' # This example uses the ssHippo dataset which you can download
#' # using the SeuratData package.
#' library(SeuratData)
#' data('ssHippo')
#' # perform filtering of beads
#' ssHippo.filtered <- FilterSlideSeq(ssHippo, radius = 2300)
#' # This radius looks to small so increase and repeat until satisfied
#' }
#' @export
#'
FilterSlideSeq <- function(
  object,
  image = "image",
  center = NULL,
  radius = NULL,
  do.plot = TRUE
) {
  if (!inherits(x = object[[image]], what = "SlideSeq")) {
    warning(
      "This fxn is intended for filtering SlideSeq data and is untested ",
      "outside of that context."
    )
  }
  dat <- GetTissueCoordinates(object[[image]])
  if (is.null(x = center)) {
    # heuristic for determining center of puck
    center <- c()
    x.vals <- dat[, 1]
    center[1] <- mean(
      x = x.vals[x.vals < quantile(x = x.vals, probs = 0.99) &
                   x.vals > quantile(x = x.vals, probs = 0.01)]
    )
    y.vals <- dat[, 2]
    center[2] <- mean(
      x = y.vals[y.vals < quantile(x = y.vals, probs = 0.99) &
                   y.vals > quantile(x = y.vals, probs = 0.01)]
    )
  }
  if (is.null(x = radius)) {
    stop("Please provide a radius.")
  }
  dists <- apply(X = dat, MARGIN = 1, FUN = function(x) {
    as.numeric(dist(rbind(x[c(1, 2)], center)))
  })
  cells.to.remove <- names(x = which(x = (dists > radius)))
  if (do.plot) {
    Idents(object) <- "keep"
    object <- SetIdent(object = object, cells = cells.to.remove, value = "remove")
    print(SpatialDimPlot(object = object))
  }
  return(subset(x = object, cells = cells.to.remove, invert = TRUE))
}

#' Get integration data
#'
#' @param object Seurat object
#' @param integration.name Name of integration object
#' @param slot Which slot in integration object to get
#'
#' @return Returns data from the requested slot within the integrated object
#'
#' @export
#' @concept objects
#'
GetIntegrationData <- function(object, integration.name, slot) {
  tools <- slot(object = object, name = 'tools')
  if (!(integration.name %in% names(tools))) {
    stop('Requested integration key does not exist')
  }
  int.data <- tools[[integration.name]]
  return(slot(object = int.data, name = slot))
}

#' Set integration data
#'
#' @param object Seurat object
#' @param integration.name Name of integration object
#' @param slot Which slot in integration object to set
#' @param new.data New data to insert
#'
#' @return Returns a \code{\link{Seurat}} object
#'
#' @export
#' @concept objects
#'
SetIntegrationData <- function(object, integration.name, slot, new.data) {
  tools <- slot(object = object, name = 'tools')
  if (!(integration.name %in% names(tools))) {
    new.integrated <- new(Class = 'IntegrationData')
    slot(object = new.integrated, name = slot) <- new.data
    tools[[integration.name]] <- new.integrated
    slot(object = object, name = 'tools') <- tools
    return(object)
  }
  int.data <- tools[[integration.name]]
  slot(object = int.data, name = slot) <- new.data
  tools[[integration.name]] <- int.data
  slot(object = object, name = 'tools') <- tools
  return(object)
}

#' Splits object into a list of subsetted objects.
#'
#' Splits object based on a single attribute into a list of subsetted objects,
#' one for each level of the attribute. For example, useful for taking an object
#' that contains cells from many patients, and subdividing it into
#' patient-specific objects.
#'
#' @param object Seurat object
#' @param split.by Attribute for splitting. Default is "ident". Currently
#' only supported for class-level (i.e. non-quantitative) attributes.
#'
#' @return A named list of Seurat objects, each containing a subset of cells
#' from the original object.
#'
#' @export
#' @concept objects
#'
#' @examples
#' data("pbmc_small")
#' # Assign the test object a three level attribute
#' groups <- sample(c("group1", "group2", "group3"), size = 80, replace = TRUE)
#' names(groups) <- colnames(pbmc_small)
#' pbmc_small <- AddMetaData(object = pbmc_small, metadata = groups, col.name = "group")
#' obj.list <- SplitObject(pbmc_small, split.by = "group")
#'
SplitObject <- function(object, split.by = "ident") {
  if (split.by == 'ident') {
    groupings <- Idents(object = object)
  } else {
    groupings <- FetchData(object = object, vars = split.by)[, 1]
  }
  groupings <- unique(x = as.character(x = groupings))
  obj.list <- list()
  for (i in groupings) {
    if (split.by == "ident") {
      obj.list[[i]] <- subset(x = object, idents = i)
    }
    else {
      cells <- which(x = object[[split.by, drop = TRUE]] == i)
      cells <- colnames(x = object)[cells]
      obj.list[[i]] <- subset(x = object, cells = cells)
    }
  }
  return(obj.list)
}

#' Find features with highest scores for a given dimensional reduction technique
#'
#' Return a list of features with the strongest contribution to a set of components
#'
#' @param object DimReduc object
#' @param dim Dimension to use
#' @param nfeatures Number of features to return
#' @param projected Use the projected feature loadings
#' @param balanced Return an equal number of features with both + and - scores.
#' @param ... Extra parameters passed to \code{\link{Loadings}}
#'
#' @return Returns a vector of features
#'
#' @export
#' @concept objects
#'
#' @examples
#' data("pbmc_small")
#' pbmc_small
#' TopFeatures(object = pbmc_small[["pca"]], dim = 1)
#' # After projection:
#' TopFeatures(object = pbmc_small[["pca"]], dim = 1,  projected = TRUE)
#'
TopFeatures <- function(
  object,
  dim = 1,
  nfeatures = 20,
  projected = FALSE,
  balanced = FALSE,
  ...
) {
  loadings <- Loadings(object = object, projected = projected, ...)[, dim, drop = FALSE]
  return(Top(
    data = loadings,
    num = nfeatures,
    balanced = balanced
  ))
}

#' Find cells with highest scores for a given dimensional reduction technique
#'
#' Return a list of genes with the strongest contribution to a set of components
#'
#' @param object DimReduc object
#' @param dim Dimension to use
#' @param ncells Number of cells to return
#' @param balanced Return an equal number of cells with both + and - scores.
#' @param ... Extra parameters passed to \code{\link{Embeddings}}
#'
#' @return Returns a vector of cells
#'
#' @export
#' @concept objects
#'
#' @examples
#' data("pbmc_small")
#' pbmc_small
#' head(TopCells(object = pbmc_small[["pca"]]))
#' # Can specify which dimension and how many cells to return
#' TopCells(object = pbmc_small[["pca"]], dim = 2, ncells = 5)
#'
TopCells <- function(object, dim = 1, ncells = 20, balanced = FALSE, ...) {
  embeddings <- Embeddings(object = object, ...)[, dim, drop = FALSE]
  return(Top(
    data = embeddings,
    num = ncells,
    balanced = balanced
  ))
}

#' Get nearest neighbors for given cell
#'
#' Return a vector of cell names of the nearest n cells.
#'
#' @param object \code{\link{Neighbor}} object
#' @param cell Cell of interest
#' @param n Number of neighbors to return
#'
#' @return Returns a vector of cell names
#'
#' @export
#' @concept objects
#'
TopNeighbors <- function(object, cell, n = 5) {
  indices <- Indices(object = object)[cell, 1:n]
  return(Cells(x = object)[indices])
}

#%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%
# Methods for Seurat-defined generics
#%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%

#' @param assay Assay to convert
#' @param reduction Name of DimReduc to set to main reducedDim in cds
#'
#' @rdname as.CellDataSet
#' @concept objects
#' @export
#' @method as.CellDataSet Seurat
#'
as.CellDataSet.Seurat <- function(x, assay = NULL, reduction = NULL, ...) {
  CheckDots(...)
  if (!PackageCheck('monocle', error = FALSE)) {
    stop("Please install monocle from Bioconductor before converting to a CellDataSet object")
  } else if (packageVersion(pkg = 'monocle') >= package_version(x = '2.99.0')) {
    stop("Seurat can only convert to/from Monocle v2.X objects")
  }
  assay <- assay %||% DefaultAssay(object = x)
  # make variables, then run `newCellDataSet`
  # create cellData counts
  counts <- GetAssayData(object = x, assay = assay, slot = "counts")
  # metadata
  cell.metadata <- x[[]]
  feature.metadata <- x[[assay]][[]]
  if (!"gene_short_name" %in% colnames(x = feature.metadata)) {
    feature.metadata$gene_short_name <- rownames(x = feature.metadata)
  }
  pd <- new(Class = "AnnotatedDataFrame", data = cell.metadata)
  fd <- new(Class = "AnnotatedDataFrame", data = feature.metadata)
  # Now, determine the expressionFamily
  if ("monocle" %in% names(x = Misc(object = x))) {
    expressionFamily <- Misc(object = x, slot = "monocle")[["expressionFamily"]]
  } else {
    if (all(counts == floor(x = counts))) {
      expressionFamily <- VGAM::negbinomial.size()
    } else if (any(counts < 0)) {
      expressionFamily <- VGAM::uninormal()
    } else {
      expressionFamily <- VGAM::tobit()
    }
  }
  cds <- monocle::newCellDataSet(
    cellData = counts,
    phenoData = pd,
    featureData = fd,
    expressionFamily = expressionFamily
  )
  if ("monocle" %in% names(x = Misc(object = x))) {
    monocle::cellPairwiseDistances(cds = cds) <- Misc(object = x, slot = "monocle")[["cellPairwiseDistances"]]
    monocle::minSpanningTree(cds = cds) <- Misc(object = x, slot = "monocle")[["minSpanningTree"]]
    Biobase::experimentData(cds = cds) <- Misc(object = x, slot = "monocle")[["experimentData"]]
    Biobase::protocolData(cds = cds) <- Misc(object = x, slot = "monocle")[["protocolData"]]
    Biobase::classVersion(cds = cds) <- Misc(object = x, slot = "monocle")[["classVersion"]]
    # no setter methods found for following slots
    slot(object = cds, name = "lowerDetectionLimit") <- Misc(object = x, slot = "monocle")[["lowerDetectionLimit"]]
    slot(object = cds, name = "dispFitInfo") <- Misc(object = x, slot = "monocle")[["dispFitInfo"]]
    slot(object = cds, name = "auxOrderingData") <- Misc(object = x, slot = "monocle")[["auxOrderingData"]]
    slot(object = cds, name = "auxClusteringData") <- Misc(object = x, slot = "monocle")[["auxClusteringData"]]
  }
  # adding dimensionality reduction data to the CDS
  dr.slots <- c("reducedDimS", "reducedDimK", "reducedDimW", "reducedDimA")
  reduction <- reduction %||% DefaultDimReduc(object = x, assay = assay)
  if (!is.null(x = reduction)) {
    if (grepl(pattern = 'tsne', x = tolower(x = reduction))) {
      slot(object = cds, name = "dim_reduce_type") <- "tSNE"
      monocle::reducedDimA(cds = cds) <- t(x = Embeddings(object = x[[reduction]]))
    } else {
      slot(object = cds, name = "dim_reduce_type") <- reduction
      monocle::reducedDimA(cds = cds) <- Loadings(object = x[[reduction]])
      slot(object = cds, name = "reducedDimS") <- Embeddings(object = x[[reduction]])
    }
    for (ii in dr.slots) {
      if (ii %in% names(x = slot(object = x[[reduction]], name = "misc"))) {
        slot(object = cds, name = ii) <- slot(object = x[[reduction]], name = "misc")[[ii]]
      }
    }
  }
  return(cds)
}

#' Convert objects to \code{Seurat} objects
#'
#' @inheritParams SeuratObject::as.Seurat
#' @param slot Slot to store expression data as
#' @param verbose Show progress updates
#'
#' @return A \code{Seurat} object generated from \code{x}
#'
#' @importFrom utils packageVersion
#'
#' @rdname as.Seurat
#' @concept objects
#' @export
#' @method as.Seurat CellDataSet
#'
#' @seealso \code{\link[SeuratObject:as.Seurat]{SeuratObject::as.Seurat}}
#'
as.Seurat.CellDataSet <- function(
  x,
  slot = 'counts',
  assay = 'RNA',
  verbose = TRUE,
  ...
) {
  CheckDots(...)
  if (!PackageCheck('monocle', error = FALSE)) {
    stop("Please install monocle from Bioconductor before converting to a CellDataSet object")
  } else if (packageVersion(pkg = 'monocle') >= package_version(x = '2.99.0')) {
    stop("Seurat can only convert to/from Monocle v2.X objects")
  }
  slot <- match.arg(arg = slot, choices = c('counts', 'data'))
  if (verbose) {
    message("Pulling expression data")
  }
  expr <- Biobase::exprs(object = x)
  if (IsMatrixEmpty(x = expr)) {
    stop("No data provided in this CellDataSet object", call. = FALSE)
  }
  meta.data <- as.data.frame(x = Biobase::pData(object = x))
  # if cell names are NULL, fill with cell_X
  if (is.null(x = colnames(x = expr))) {
    warning(
      "The column names of the 'counts' and 'data' matrices are NULL. Setting cell names to cell_columnidx (e.g 'cell_1').",
      call. = FALSE,
      immediate. = TRUE
    )
    rownames(x = meta.data) <- colnames(x = expr) <- paste0("cell_", 1:ncol(x = expr))
  }
  # Creating the object
  if (verbose) {
    message("Building Seurat object")
  }
  if (slot == 'data') {
    assays <- list(CreateAssayObject(data = expr))
    names(x = assays) <- assay
    Key(object = assays[[assay]]) <- suppressWarnings(expr = UpdateKey(key = assay))
    object <- new(
      Class = 'Seurat',
      assays = assays,
      meta.data = meta.data,
      version = packageVersion(pkg = 'Seurat'),
      project.name = 'SeuratProject'
    )
    DefaultAssay(object = object) <- assay
  } else {
    object <- CreateSeuratObject(
      counts = expr,
      meta.data = meta.data,
      assay = assay
    )
  }
  # feature metadata
  if (verbose) {
    message("Adding feature-level metadata")
  }
  feature.metadata <- Biobase::fData(object = x)
  object[[assay]][[names(x = feature.metadata)]] <- feature.metadata
  # mean/dispersion values
  disp.table <- tryCatch(
    expr = suppressWarnings(expr = monocle::dispersionTable(cds = x)),
    error = function(...) {
      return(NULL)
    }
  )
  if (!is.null(x = disp.table)) {
    if (verbose) {
      message("Adding dispersion information")
    }
    rownames(x = disp.table) <- disp.table[, 1]
    disp.table[, 1] <- NULL
    colnames(x = disp.table) <- paste0('monocle_', colnames(x = disp.table))
    object[[assay]][[names(x = disp.table)]] <- disp.table
  } else if (verbose) {
    message("No dispersion information in CellDataSet object")
  }
  # variable features
  if ("use_for_ordering" %in% colnames(x = feature.metadata)) {
    if (verbose) {
      message("Setting variable features")
    }
    VariableFeatures(object = object, assay = assay) <- rownames(x = feature.metadata)[which(x = feature.metadata[, "use_for_ordering"])]
  } else if (verbose) {
    message("No variable features present")
  }
  # add dim reduction
  dr.name <- slot(object = x, name = "dim_reduce_type")
  if (length(x = dr.name) > 0) {
    if (verbose) {
      message("Adding ", dr.name, " dimensional reduction")
    }
    reduced.A <- t(x = slot(object = x, name = 'reducedDimA'))
    reduced.S <- t(x = slot(object = x, name = 'reducedDimS'))
    if (IsMatrixEmpty(x = reduced.S)) {
      embeddings <- reduced.A
      loadings <- new(Class = 'matrix')
    } else {
      embeddings <- reduced.S
      loadings <- t(x = reduced.A)
    }
    rownames(x = embeddings) <- colnames(x = object)
    misc.dr <- list(
      reducedDimS = slot(object = x, name = "reducedDimS"),
      reducedDimK = slot(object = x, name = "reducedDimK"),
      reducedDimW = slot(object = x, name = "reducedDimW"),
      reducedDimA = slot(object = x, name = "reducedDimA")
    )
    dr <- suppressWarnings(expr = CreateDimReducObject(
      embeddings = embeddings,
      loadings = loadings,
      assay = assay,
      key = UpdateKey(key = tolower(x = dr.name)),
      misc = misc.dr
    ))
    object[[dr.name]] <- dr
  } else if (verbose) {
    message("No dimensional reduction information found")
  }
  monocle.specific.info <- list(
    expressionFamily = slot(object = x, name = "expressionFamily"),
    lowerDetectionLimit = slot(object = x, name = "lowerDetectionLimit"),
    dispFitInfo = slot(object = x, name = "dispFitInfo"),
    cellPairwiseDistances = slot(object = x, name = "cellPairwiseDistances"),
    minSpanningTree = slot(object = x, name = "minSpanningTree"),
    auxOrderingData = slot(object = x, name = "auxOrderingData"),
    auxClusteringData = slot(object = x, name = "auxClusteringData"),
    experimentData = slot(object = x, name = "experimentData"),
    protocolData = slot(object = x, name = "protocolData"),
    classVersion = slot(object = x, name = ".__classVersion__")
  )
  Misc(object = object, slot = "monocle")  <- monocle.specific.info
  return(object)
}

#' @param counts name of the SingleCellExperiment assay to store as \code{counts};
#' set to \code{NULL} if only normalized data are present
#' @param data name of the SingleCellExperiment assay to slot as \code{data}.
#' Set to NULL if only counts are present
#' @param assay Name to store expression matrices as
#' @param project Project name for new Seurat object
#'
#' @rdname as.Seurat
#' @concept objects
#' @export
#' @method as.Seurat SingleCellExperiment
#'
as.Seurat.SingleCellExperiment <- function(
  x,
  counts = 'counts',
  data = 'logcounts',
  assay = 'RNA',
  project = 'SingleCellExperiment',
  ...
) {
  CheckDots(...)
  if (!PackageCheck('SingleCellExperiment', error = FALSE)) {
    stop(
      "Please install SingleCellExperiment from Bioconductor before converting to a SingeCellExperiment object",
      call. = FALSE
    )
  }
  meta.data <- as.data.frame(x = SummarizedExperiment::colData(x = x))
  # Pull expression matrices
  mats <- list(counts = counts, data = data)
  mats <- Filter(f = Negate(f = is.null), x = mats)
  if (length(x = mats) == 0) {
    stop("Cannot pass 'NULL' to both 'counts' and 'data'")
  }
  for (m in 1:length(x = mats)) {
    # if (is.null(x = mats[[m]])) next
    mats[[m]] <- tryCatch(
      expr = SummarizedExperiment::assay(x = x, i = mats[[m]]),
      error = function(e) {
        stop("No data in provided assay - ", mats[[m]], call. = FALSE)
      }
    )
    # if cell names are NULL, fill with cell_X
    if (is.null(x = colnames(x = mats[[m]]))) {
      warning(
        "The column names of the",
        names(x = mats)[m],
        " matrix is NULL. Setting cell names to cell_columnidx (e.g 'cell_1').",
        call. = FALSE,
        immediate. = TRUE
      )
      cell.names <- paste0("cell_", 1:ncol(x = mats[[m]]))
      colnames(x = mats[[m]]) <- cell.names
      rownames(x = meta.data) <- cell.names
    }
  }
  assays <- if (is.null(x = mats$counts)) {
    list(CreateAssayObject(data = mats$data))
  } else if (is.null(x = mats$data)) {
    list(CreateAssayObject(counts = mats$counts))
  } else {
    a <- CreateAssayObject(counts = mats$counts)
    a <- SetAssayData(object = a, slot = 'data', new.data = mats$data)
    list(a)
  }
  names(x = assays) <- assay
  Key(object = assays[[assay]]) <- paste0(tolower(x = assay), '_')
  # Create the Seurat object
  object <- new(
    Class = 'Seurat',
    assays = assays,
    meta.data = meta.data,
    version = packageVersion(pkg = 'Seurat'),
    project.name = project
  )
  DefaultAssay(object = object) <- assay
  Idents(object = object) <- project
  # Get DimReduc information
  if (length(x = SingleCellExperiment::reducedDimNames(x = x)) > 0) {
    for (dr in SingleCellExperiment::reducedDimNames(x = x)) {
      embeddings <- SingleCellExperiment::reducedDim(x = x, type = dr)
      if (is.null(x = rownames(x = embeddings))) {
        rownames(x = embeddings)  <- cell.names
      }
      key <- gsub(
        pattern = "[[:digit:]]",
        replacement = "_",
        x = colnames(x = SingleCellExperiment::reducedDim(x = x, type = dr))[1]
      )
      if (length(x = key) == 0) {
        key <- paste0(dr, "_")
      }
      colnames(x = embeddings) <- paste0(key, 1:ncol(x = embeddings))
      object[[dr]] <- CreateDimReducObject(
        embeddings = embeddings,
        key = key,
        assay = DefaultAssay(object = object)
      )
    }
  }
  return(object)
}

#' @param assay Assay to convert
#'
#' @rdname as.SingleCellExperiment
#' @concept objects
#' @export
#' @method as.SingleCellExperiment Seurat
#'
as.SingleCellExperiment.Seurat <- function(x, assay = NULL, ...) {
  CheckDots(...)
  if (!PackageCheck('SingleCellExperiment', error = FALSE)) {
    stop("Please install SingleCellExperiment from Bioconductor before converting to a SingeCellExperiment object")
  }
  assay <- assay %||% DefaultAssay(object = x)
  assays = list(
    counts = GetAssayData(object = x, assay = assay, slot = "counts"),
    logcounts = GetAssayData(object = x, assay = assay, slot = "data")
  )
  assays <- assays[sapply(X = assays, FUN = nrow) != 0]
  sce <- SingleCellExperiment::SingleCellExperiment(assays = assays)
  metadata <- x[[]]
  metadata$ident <- Idents(object = x)
  SummarizedExperiment::colData(sce) <- S4Vectors::DataFrame(metadata)
  SummarizedExperiment::rowData(sce) <- S4Vectors::DataFrame(x[[assay]][[]])
  for (dr in FilterObjects(object = x, classes.keep = "DimReduc")) {
    SingleCellExperiment::reducedDim(sce, toupper(x = dr)) <- Embeddings(object = x[[dr]])
  }
  return(sce)
}

#' Cast to Sparse
#'
#' @inheritParams SeuratObject::as.sparse
#'
#' @importFrom methods is
#' @importFrom Matrix sparseMatrix
#'
#' @rdname as.sparse
#' @concept objects
#' @export
#' @method as.sparse H5Group
#'
#'
#' @seealso \code{\link[SeuratObject:as.sparse]{SeuratObject::as.sparse}}
#'
as.sparse.H5Group <- function(x, ...) {
  CheckDots(...)
  for (i in c('data', 'indices', 'indptr')) {
    if (!x$exists(name = i) || !is(object = x[[i]], class2 = 'H5D')) {
      stop("Invalid H5Group specification for a sparse matrix, missing dataset ", i)
    }
  }
  if ('h5sparse_shape' %in% hdf5r::h5attr_names(x = x)) {
    return(sparseMatrix(
      i = x[['indices']][] + 1,
      p = x[['indptr']][],
      x = x[['data']][],
      dims = rev(x = hdf5r::h5attr(x = x, which = 'h5sparse_shape'))
    ))
  }
  return(sparseMatrix(
    i = x[['indices']][] + 1,
    p = x[['indptr']][],
    x = x[['data']][]
  ))
}

#' Get Cell Names
#'
#' @inheritParams SeuratObject::Cells
#'
#' @rdname Cells
#' @concept objects
#' @method Cells SCTModel
#' @export
#'
Cells.SCTModel <- function(x) {
  return(rownames(x = slot(object = x, name = "cell.attributes")))
}

#' @rdname Cells
#' @concept objects
#' @method Cells SlideSeq
#' @export
#'
#' @seealso \code{\link[SeuratObject:Cells]{SeuratObject::Cells}}
#'
Cells.SlideSeq <- function(x) {
  return(rownames(x = GetTissueCoordinates(object = x)))
}

#' @rdname Cells
#' @concept objects
#' @method Cells STARmap
#' @export
#'
Cells.STARmap <- function(x) {
  return(rownames(x = GetTissueCoordinates(object = x)))
}

#' @rdname Cells
#' @concept objects
#' @method Cells VisiumV1
#' @export
#'
Cells.VisiumV1 <- function(x) {
  return(rownames(x = GetTissueCoordinates(object = x, scale = NULL)))
}


#' @param assay Assay to get
#'
#' @rdname GetAssay
#' @concept objects
#' @export
#' @method GetAssay Seurat
#'
#' @examples
#' data("pbmc_small")
#' GetAssay(object = pbmc_small, assay = "RNA")
#'
GetAssay.Seurat <- function(object, assay = NULL, ...) {
  CheckDots(...)
  assay <- assay %||% DefaultAssay(object = object)
  object.assays <- FilterObjects(object = object, classes.keep = 'Assay')
  if (!assay %in% object.assays) {
    stop(paste0(
      assay,
      " is not an assay present in the given object. Available assays are: ",
      paste(object.assays, collapse = ", ")
    ))
  }
  return(slot(object = object, name = 'assays')[[assay]])
}


#' Get Image Data
#'
#' @inheritParams SeuratObject::GetImage
#'
#' @rdname GetImage
#' @method GetImage SlideSeq
#' @concept objects
#' @export
#'
#' @seealso \code{\link[SeuratObject:GetImage]{SeuratObject::GetImage}}
#'
GetImage.SlideSeq <- function(
  object,
  mode = c('grob', 'raster', 'plotly', 'raw'),
  ...
) {
  mode <- match.arg(arg = mode)
  return(NullImage(mode = mode))
}

#' @rdname GetImage
#' @method GetImage STARmap
#' @concept objects
#' @export
#'
GetImage.STARmap <- function(
  object,
  mode = c('grob', 'raster', 'plotly', 'raw'),
  ...
) {
  mode <- match.arg(arg = mode)
  return(NullImage(mode = mode))
}

#' @importFrom plotly raster2uri
#' @importFrom grDevices as.raster
#' @importFrom grid rasterGrob unit
#'
#' @rdname GetImage
#' @concept objects
#' @method GetImage VisiumV1
#' @export
#'
GetImage.VisiumV1 <- function(
  object,
  mode = c('grob', 'raster', 'plotly', 'raw'),
  ...
) {
  mode <- match.arg(arg = mode)
  image <- slot(object = object, name = 'image')
  image <- switch(
    EXPR = mode,
    'grob' = rasterGrob(
      image = image,
      width = unit(x = 1, units = 'npc'),
      height = unit(x = 1, units = 'npc')
    ),
    'raster' = as.raster(x = image),
    'plotly' = list(
      source = raster2uri(r = GetImage(object = object, mode = 'raster')),
      xref = 'x',
      yref = 'y',
      # x = -7,
      # y = -7,
      sizex = ncol(x = object),
      sizey = nrow(x = object),
      sizing = 'stretch',
      opacity = 1,
      layer = 'below'
    ),
    'raw' = image,
    stop("Unknown image mode: ", mode, call. = FALSE)
  )
  return(image)
}

#' Get Tissue Coordinates
#'
#' @inheritParams SeuratObject::GetTissueCoordinates
#'
#' @rdname GetTissueCoordinates
#' @method GetTissueCoordinates SlideSeq
#' @concept objects
#' @export
#'
#' @seealso \code{\link[SeuratObject:GetTissueCoordinates]{SeuratObject::GetTissueCoordinates}}
#'
GetTissueCoordinates.SlideSeq <- function(object, ...) {
  coords <- slot(object = object, name = 'coordinates')
  colnames(x = coords) <- c('x', 'y')
  # coords$y <- -rev(x = coords$y) + 1
  # coords$y <- FlipCoords(x = coords$y)
  coords$cells <- rownames(x = coords)
  return(coords)
}

#' @param qhulls return qhulls instead of centroids
#'
#' @rdname GetTissueCoordinates
#' @method GetTissueCoordinates STARmap
#' @concept objects
#' @export
#'
GetTissueCoordinates.STARmap <- function(object, qhulls = FALSE, ...) {
  if (qhulls) {
    return(slot(object = object, name = 'qhulls'))
  }
  return(slot(object = object, name = 'coordinates'))
}

#' @param scale A factor to scale the coordinates by; choose from: 'tissue',
#' 'fiducial', 'hires', 'lowres', or \code{NULL} for no scaling
#' @param cols Columns of tissue coordinates data.frame to pull
#'
#' @rdname GetTissueCoordinates
#' @method GetTissueCoordinates VisiumV1
#' @concept objects
#' @export
#'
GetTissueCoordinates.VisiumV1 <- function(
  object,
  scale = 'lowres',
  cols = c('imagerow', 'imagecol'),
  ...
) {
  cols <- cols %||% colnames(x = slot(object = object, name = 'coordinates'))
  if (!is.null(x = scale)) {
    coordinates <- slot(object = object, name = 'coordinates')[, c('imagerow', 'imagecol')]
    scale <- match.arg(arg = scale, choices = c('spot', 'fiducial', 'hires', 'lowres'))
    scale.use <- ScaleFactors(object = object)[[scale]]
    coordinates <- coordinates * scale.use
  } else {
    coordinates <- slot(object = object, name = 'coordinates')[, cols]
  }
  return(coordinates)
}

#' Get Spot Radius
#'
#' @inheritParams SeuratObject::Radius
#'
#' @rdname Radius
#' @concept objects
#' @method Radius SlideSeq
#' @export
#'
#' @seealso \code{\link[SeuratObject:Radius]{SeuratObject::Radius}}
#'
Radius.SlideSeq <- function(object) {
  return(0.005)
}

#' @rdname Radius
#' @concept objects
#' @method Radius STARmap
#' @export
#'
Radius.STARmap <- function(object) {
  return(NULL)
}

#' @rdname Radius
#' @concept objects
#' @method Radius VisiumV1
#' @export
#'
Radius.VisiumV1 <- function(object) {
  return(slot(object = object, name = 'spot.radius'))
}

#' @rdname RenameCells
#' @export
#' @method RenameCells SCTAssay
#'
RenameCells.SCTAssay <- function(object, new.names = NULL, ...) {
  CheckDots(...)
  old.names <- Cells(x = object)
  names(x = new.names) <- old.names
  cell.attributes <- SCTResults(object = object, slot = "cell.attributes")
  if (length(x = cell.attributes) > 0) {
    if (is.data.frame(x = cell.attributes)) {
      old.names <- rownames(x = cell.attributes)
      rownames(x = cell.attributes) <- unname(obj = new.names[old.names])
    } else {
      cell.attributes <- lapply(
        X = cell.attributes,
        FUN = function(x) {
          old.names <- rownames(x = x)
          rownames(x = x) <- unname(obj = new.names[old.names])
          return(x)
        }
      )
    }
    SCTResults(object = object, slot = "cell.attributes") <- cell.attributes
  }
  new.names <- unname(obj = new.names)
  object <- NextMethod()
  return(object)
}

#' Rename Cells in an Object
#'
#' @inheritParams SeuratObject::RenameCells
#'
#' @rdname RenameCells
#' @method RenameCells SlideSeq
#' @export
#'
#' @seealso \code{\link[SeuratObject:RenameCells]{SeuratObject::RenameCells}}
#'
RenameCells.SlideSeq <- function(object, new.names = NULL, ...) {
  return(RenameCells.VisiumV1(object = object, new.names = new.names))
}

#' @rdname RenameCells
#' @method RenameCells STARmap
#' @export
#'
RenameCells.STARmap <- function(object, new.names = NULL, ...) {
  names(x = new.names) <- Cells(x = object)
  object <- RenameCells.VisiumV1(object = object, new.names = new.names)
  qhulls <- GetTissueCoordinates(object = object, qhull = TRUE)
  qhulls$cell <- new.names[qhulls$cell]
  slot(object = object, name = "qhulls") <- qhulls
  return(object)
}

#' @rdname RenameCells
#' @method RenameCells VisiumV1
#' @export
#'
RenameCells.VisiumV1 <- function(object, new.names = NULL, ...) {
  if (is.null(x = new.names)) {
    return(object)
  } else if (length(x = new.names) != length(x = Cells(x = object))) {
    stop("Wrong number of cell/spot names", call. = FALSE)
  }
  names(x = new.names) <- Cells(x = object)
  coordinates <- GetTissueCoordinates(object = object, scale = NULL, cols = NULL)
  rownames(x = coordinates) <- new.names[rownames(x = coordinates)]
  slot(object = object, name = 'coordinates') <- coordinates
  return(object)
}

#' @rdname SCTResults
#' @export
#' @method SCTResults SCTModel
#'
SCTResults.SCTModel <- function(object, slot, ...) {
  CheckDots(...)
  slots.use <- c('feature.attributes', 'cell.attributes', 'clips','umi.assay',  'model', 'arguments')
  if (!slot %in% slots.use) {
    stop(
      "'slot' must be one of ",
      paste(slots.use, collapse = ', '),
      call. = FALSE
    )
  }
  return(slot(object = object, name = slot))
}

#' @rdname SCTResults
#' @export
#' @method SCTResults<- SCTModel
#'
"SCTResults<-.SCTModel" <- function(object, slot, ..., value) {
  slots.use <- c('feature.attributes', 'cell.attributes', 'clips','umi.assay', 'model', 'arguments')
  if (!slot %in% slots.use) {
    stop(
      "'slot' must be one of ",
      paste(slots.use, collapse = ', '),
      call. = FALSE
    )
  }
  slot(object = object, name = slot) <- value
  return(object)
}

#' @param slot Which slot to pull the SCT results from
#' @param model Name of SCModel to pull result from. Available names can be
#' retrieved with \code{levels}.
#'
#' @return Returns the value present in the requested slot for the requested
#' group. If group is not specified, returns a list of slot results for each
#' group unless there is only one group present (in which case it just returns
#' the slot directly).
#'
#' @rdname SCTResults
#' @export
#' @method SCTResults SCTAssay
#'
SCTResults.SCTAssay <- function(object, slot, model = NULL, ...) {
  CheckDots(...)
  slots.use <- c('feature.attributes', 'cell.attributes', 'clips','umi.assay',  'model', 'arguments')
  if (!slot %in% slots.use) {
    stop(
      "'slot' must be one of ",
      paste(slots.use, collapse = ', '),
      call. = FALSE
    )
  }
  model <- model %||% levels(x = object)
  model.list <- slot(object = object, name = "SCTModel.list")[model]
  results.list <- lapply(X = model.list, FUN = function(x) SCTResults(object = x, slot = slot))
  if (length(x = results.list) == 1) {
    results.list <- results.list[[1]]
  }
  return(results.list)
}

#' @rdname SCTResults
#' @export
#' @method SCTResults<- SCTAssay
#'
"SCTResults<-.SCTAssay" <- function(object, slot, model = NULL, ..., value) {
  slots.use <- c('feature.attributes', 'cell.attributes', 'clips','umi.assay', 'model', 'arguments')
  if (!slot %in% slots.use) {
    stop(
      "'slot' must be one of ",
      paste(slots.use, collapse = ', '),
      call. = FALSE
    )
  }
  model <- model %||% levels(x = object)
  model.list <- slot(object = object, name = "SCTModel.list")[model]
  if (!is.list(x = value) | is.data.frame(x = value)) {
    value <- list(value)
  }
  model.names <- names(x = model.list)
  model.list <- lapply(
    X = 1:length(x = model.list),
    FUN = function(x) {
      SCTResults(object = model.list[[x]], slot = slot) <- value[[x]]
      return(model.list[[x]])
    }
  )
  names(x = model.list) <- model.names
  slot(object = object, name = "SCTModel.list")[model.names] <- model.list
  return(object)
}

#' @param assay Assay in the Seurat object to pull from
#'
#' @rdname SCTResults
#' @export
#' @method SCTResults Seurat
#'
SCTResults.Seurat <- function(object, assay = "SCT", slot, model = NULL, ...) {
  CheckDots(...)
  return(SCTResults(object = object[[assay]], slot = slot, model = model, ...))
}

#' @rdname ScaleFactors
#' @method ScaleFactors VisiumV1
#' @export
#'
ScaleFactors.VisiumV1 <- function(object, ...) {
  return(slot(object = object, name = 'scale.factors'))
}

#' @rdname ScaleFactors
#' @method ScaleFactors VisiumV1
#' @export
#'
ScaleFactors.VisiumV1 <- function(object, ...) {
  return(slot(object = object, name = 'scale.factors'))
}

#%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%
# Methods for R-defined generics
#%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%

#' @method [ SlideSeq
#' @concept objects
#' @export
#'
"[.SlideSeq" <- function(x, i, ...) {
  return(subset(x = x, cells = i, ...))
}

#' @method [ VisiumV1
#' @export
#'
"[.VisiumV1" <- function(x, i, ...) {
  return(subset(x = x, cells = i))
}

#' @method dim SlideSeq
#' @concept objects
#' @export
#'
dim.SlideSeq <- function(x) {
  # return(dim(x = GetImage(object = x, mode = 'raw')))
  return(c(599, 600))
}

#' @method dim STARmap
#' @concept objects
#' @export
#'
dim.STARmap <- function(x) {
  coords <- GetTissueCoordinates(object = x)
  return(c(
    max(coords[, 1]) - min(coords[, 1]),
    max(coords[, 2]) - min(coords[, 2])
  ))
}

#' @method dim VisiumV1
#' @concept objects
#' @export
#'
dim.VisiumV1 <- function(x) {
  return(dim(x = GetImage(object = x)$raster))
}


#' @rdname SCTAssay-class
#' @name SCTAssay-class
#'
#' @section Get and set SCT model names:
#' SCT results are named by initial run of \code{\link{SCTransform}} in order
#' to keep SCT parameters straight between runs. When working with merged
#' \code{SCTAssay} objects, these model names are important. \code{levels}
#' allows querying the models present. \code{levels<-} allows the changing of
#' the names of the models present, useful when merging \code{SCTAssay} objects.
#' Note: unlike normal \code{\link[base]{levels<-}}, \code{levels<-.SCTAssay}
#' allows complete changing of model names, not reordering.
#'
#' @param x An \code{SCTAssay} object
#'
#' @return \code{levels}: SCT model names
#'
#' @export
#' @method levels SCTAssay
#'
#' @examples
#' \dontrun{
#' # Query and change SCT model names
#' levels(pbmc_small[['SCT']])
#' levels(pbmc_small[['SCT']]) <- '3'
#' levels(pbmc_small[['SCT']])
#' }
#'
levels.SCTAssay <- function(x) {
  return(names(x = slot(object = x, name = "SCTModel.list")))
}

#' @rdname SCTAssay-class
#' @name SCTAssay-class
#'
#' @param value New levels, must be in the same order as the levels present
#'
#' @return \code{levels<-}: \code{x} with updated SCT model names
#'
#' @export
#' @method levels<- SCTAssay
#'
"levels<-.SCTAssay" <- function(x, value) {
  value <- sapply(X = value, FUN = function(v) {
    if (suppressWarnings(expr = !is.na(x = as.numeric(x = v)))) {
      warning("SCTModel groups cannot be number, group is added in front of ", v)
      v <- paste0("group", v)
    }
    return (v)
  })
  # Get current levels
  levels <- levels(x = x)
  if (length(x = value) != length(x = levels)) {
    stop("Must provide a vector of length ", length(x = levels), " as new levels.", call. = FALSE)
  }
  names(x = slot(object = x, name = "SCTModel.list")) <- value
  return(x)
}

#' Merge SCTAssay objects
#'
#' @inheritParams SeuratObject::merge
#' @param na.rm If na.rm = TRUE, this will only preserve residuals that are
#' present in all SCTAssays being merged. Otherwise, missing residuals will be
#' populated with NAs.
#' @export
#' @method merge SCTAssay
#'
merge.SCTAssay <- function(
  x = NULL,
  y = NULL,
  add.cell.ids = NULL,
  merge.data = TRUE,
  na.rm = TRUE,
  ...
) {
  assays <- c(x, y)
  parent.call <- grep(pattern = "merge.Seurat", x = sys.calls())
  if (length(x = parent.call) > 0) {
    # Try and fill in missing residuals if called in the context of merge.Seurat
    all.features <- unique(x = unlist(x = lapply(X = assays, FUN = function(assay) {
      if (inherits(x = x, what = "SCTAssay")) {
        return(rownames(x = GetAssayData(object = assay, slot = "scale.data")))
      }
    })))
    if (!is.null(all.features)) {
      assays <- lapply(X = 1:length(x = assays), FUN = function(assay) {
        if (inherits(x = assays[[assay]], what = "SCTAssay")) {
          parent.environ <- sys.frame(which = parent.call[1])
          seurat.object <- parent.environ$objects[[assay]]
          seurat.object <- suppressWarnings(expr = GetResidual(object = seurat.object, features = all.features, assay = parent.environ$assay, verbose = FALSE))
          return(seurat.object[[parent.environ$assay]])
        }
        return(assays[[assay]])
      })
    }
  }
  sct.check <- sapply(X = assays, FUN = function(x) inherits(x = x, what = "SCTAssay"))
  if (any(!sct.check)) {
    warning("Attempting to merge an SCTAssay with another Assay type \n",
            "Converting all to standard Assay objects.", call. = FALSE)
    assays <- lapply(1:length(x = assays), FUN = function(x) {
      if (sct.check[x]) {
        assays[[x]] <- as(object = assays[[x]], Class = "Assay")
      }
      return(assays[[x]])
    })
    combined.assay <- merge(
        x = assays[[1]],
        y = assays[2:length(x = assays)],
        add.cell.ids = add.cell.ids,
        merge.data = merge.data
    )
    return(combined.assay)
  }
  combined.assay <- NextMethod()
  all.levels <- unlist(x = lapply(X = assays, FUN = levels))
  while (anyDuplicated(x = all.levels)) {
    levels.duplicate <- which(x = duplicated(x = all.levels))
    all.levels <- sapply(X = 1:length(x = all.levels), FUN = function(l) {
      if (l %in% levels.duplicate) {
        return(tryCatch(
          expr = as.numeric(x = all.levels[l]) + 1,
          warning = function(...) {
            make.unique(names = all.levels)[l]
          },
          error = function(...){
            make.unique(names = all.levels)[l]
          }
        ))
      } else {
        return(all.levels[l])
      }
    })
  }
  scale.data <- lapply(X = assays, FUN = function(x) {
    dat <- GetAssayData(object = x, slot = "scale.data")
    if (ncol(x = dat) == 0) {
      dat <- matrix(ncol = ncol(x = x))
    }
    return(dat)
  })
  all.features <- lapply(X = scale.data, FUN = rownames)
  if (na.rm) {
    # merge intersection of possible residuals
    scaled.features <- names(x = which(x = table(x = unlist(x = all.features)) == length(x = assays)))
    if (length(x = scaled.features) == 0) {
      scale.data <- list(new(Class = "matrix"))
    } else {
      scale.data <- lapply(X = scale.data, FUN = function(x) x[scaled.features, ])
    }
  } else {
    scaled.features <- unique(x = unlist(x = all.features))
    scale.data <- lapply(X = 1:length(x = scale.data), FUN = function(x) {
      na.features <- setdiff(x = scaled.features, y = rownames(x = scale.data[[x]]))
      na.mat <- matrix(
        data = NA,
        nrow = length(x = na.features),
        ncol = ncol(x = assays[[x]]),
        dimnames = list(na.features, colnames(x = assays[[x]]))
      )
      return(rbind(scale.data[[x]], na.mat)[scaled.features, ])
    })
  }
  scale.data <- do.call(what = cbind, args = scale.data)
  combined.assay <- SetAssayData(object = combined.assay, slot = "scale.data", new.data = scale.data)
  model.list <- unlist(x = lapply(
    X = assays,
    FUN = slot,
    name = "SCTModel.list"
  ))
  names(x = model.list) <- all.levels
  model.list <- model.list %||% list()
  combined.assay <- new(
    Class = "SCTAssay",
    combined.assay,
    SCTModel.list = model.list
  )
  return(combined.assay)
}

#' Subset an AnchorSet object
#'
#' @inheritParams base::subset
#' @param score.threshold Only anchor pairs with scores greater than this value
#' are retained.
#' @param disallowed.dataset.pairs Remove any anchors formed between the
#' provided pairs. E.g. \code{list(c(1, 5), c(1, 2))} filters out any anchors between
#' datasets 1 and 5 and datasets 1 and 2.
#' @param dataset.matrix Provide a binary matrix specifying whether a dataset
#' pair is allowable (1) or not (0). Should be a dataset x dataset matrix.
#' @param group.by Grouping variable to determine allowable ident pairs
#' @param disallowed.ident.pairs Remove any anchors formed between provided
#' ident pairs. E.g. \code{list(c("CD4", "CD8"), c("B-cell", "T-cell"))}
#' @param ident.matrix Provide a binary matrix specifying whether an ident pair
#' is allowable (1) or not (0). Should be an ident x ident symmetric matrix
#'
#' @return Returns an \code{\link{AnchorSet}} object with specified anchors
#' filtered out
#'
#' @export
#' @method subset AnchorSet
#'
subset.AnchorSet <- function(
  x,
  score.threshold = NULL,
  disallowed.dataset.pairs = NULL,
  dataset.matrix = NULL,
  group.by = NULL,
  disallowed.ident.pairs = NULL,
  ident.matrix = NULL,
  ...
) {
  if (!is.null(x = disallowed.dataset.pairs) && !is.null(x = dataset.matrix)) {
    stop("Please use either disallowed.dataset.pairs OR dataset.matrix, not both.")
  }
  # Filter based on scores
  if (!is.null(x = score.threshold)) {
    if (score.threshold > 1 | score.threshold < 0) {
      stop(
        "Anchors are scored on a scale between 0 and 1. Please provide a value",
        " in that range to score.threshold."
      )
    }
    anchors <- slot(object = x, name = "anchors")
    anchors <- anchors[anchors[, 'score'] > score.threshold, , drop = FALSE]
    slot(object = x, name = "anchors") <- anchors
  }
  object.names <- names(x = slot(object = x, name = "object.list"))
  num.obs <- length(x = object.names)
  # Filter based on dataset pairings
  if (!is.null(x = disallowed.dataset.pairs)) {
    dataset.matrix <- matrix(data = 1, nrow = num.obs, ncol = num.obs)
    for(i in 1:length(x = disallowed.dataset.pairs)) {
      pair <- disallowed.dataset.pairs[[i]]
      if (length(x = pair) != 2) {
        stop("Please ensure all list items in disallowed.dataset.pairs are of length 2.")
      }
      if (any(pair %in% object.names)) {
        pair[which(pair %in% object.names)] <- sapply(
          X = pair[which(pair %in% object.names)],
          FUN = function(x) {
            which(object.names == x)
          })
      }
      pair <- as.numeric(x = pair)
      dataset.matrix[pair[1], pair[2]] <- 0
    }
  }
  if (!is.null(x = dataset.matrix)) {
    if (any(dim(x = dataset.matrix) != c(num.obs, num.obs))){
      stop("Please provide a dataset.matrix that is ", num.obs, " x ", num.obs, ".")
    }
    anchors <- slot(object = x, name = "anchors")
    pairs <- which(dataset.matrix == 0, arr.ind = TRUE)
    for (i in 1:nrow(x = pairs)) {
      anchors <- anchors[-which(x = anchors$dataset1 == pairs[i, 1] & anchors$dataset2 == pairs[i, 2]), ]
      anchors <- anchors[-which(x = anchors$dataset1 == pairs[i, 2] & anchors$dataset2 == pairs[i, 1]), ]
    }
    slot(object = x, name = "anchors") <- anchors
  }
  # Filter based on ident pairings
  if (!is.null(x = group.by)) {
    anchors <- AnnotateAnchors(object = x, vars = group.by)
    if (!is.null(x = disallowed.ident.pairs) && !is.null(x = ident.matrix)) {
      stop("Please use either disallowed.ident.pairs OR ident.matrix, not both.")
    }
    unique.ids <- unique(x = c(anchors[, paste0("cell1.", group.by)], anchors[, paste0("cell2.", group.by)]))
    unique.ids <- unique.ids[!is.na(x = unique.ids)]
    num.ids <- length(x = unique.ids)
    if (!is.null(x = disallowed.ident.pairs)) {
      ident.matrix <- matrix(data = 1, nrow = num.ids, ncol = num.ids)
      rownames(x = ident.matrix) <- unique.ids
      colnames(x = ident.matrix) <- unique.ids
      for(i in 1:length(x = disallowed.ident.pairs)) {
        pair <- disallowed.ident.pairs[[i]]
        if (length(x = pair) != 2) {
          stop("Please ensure all list items in disallowed.dataset.pairs are of length 2.")
        }
        ident.matrix[pair[1], pair[2]] <- 0
      }
    }
    if (!is.null(x = ident.matrix)) {
      if (any(dim(x = ident.matrix) != c(num.ids, num.ids))){
        stop("Please provide a dataset.matrix that is ", num.ids, " x ", num.ids, ".")
      }
      to.remove <- c()
      pairs <- which(ident.matrix == 0, arr.ind = TRUE)
      for (i in 1:nrow(x = pairs)) {
        id1 <- rownames(x = ident.matrix)[pairs[i, 1]]
        id2 <- colnames(x = ident.matrix)[pairs[i, 2]]
        to.remove <- c(to.remove, which(x = anchors[, paste0("cell1.", group.by)] == id1 & anchors[, paste0("cell2.", group.by)] == id2))
        to.remove <- c(to.remove, which(x = anchors[, paste0("cell1.", group.by)] == id2 & anchors[, paste0("cell2.", group.by)] == id1))
      }
      anchors <- slot(object = x, name = "anchors")
      anchors <- anchors[-to.remove, ]
      slot(object = x, name = "anchors") <- anchors
    }
  }
  return(x)
}

#' @export
#' @method subset SCTAssay
#'
subset.SCTAssay <- function(x, cells = NULL, features = NULL, ...) {
  x <- NextMethod()
  models <- levels(x = x)
  for (m in models) {
    attr <- SCTResults(object = x, slot = "cell.attributes", model = m)
    attr <- attr[intersect(x = rownames(x = attr), y = Cells(x = x)), , drop = FALSE]
    SCTResults(object = x, slot = "cell.attributes", model = m) <- attr
  }
  return(x)
}

#' @method subset SlideSeq
#' @concept objects
#' @export
#'
subset.SlideSeq <- function(x, cells, ...) {
  x <- subset.VisiumV1(x = x, cells = cells, ...)
  return(x)
}

#' @method subset STARmap
#' @concept objects
#' @export
#'
subset.STARmap <- function(x, cells, ...) {
  x <- subset.VisiumV1(x = x, cells = cells, ...)
  qhulls <- GetTissueCoordinates(object = x, qhulls = TRUE)
  qhulls <- qhulls[qhulls$cell %in% cells, ]
  slot(object = x, name = 'qhulls') <- qhulls
  return(x)
}

#' @method subset VisiumV1
#' @concept objects
#' @export
#'
subset.VisiumV1 <- function(x, cells, ...) {
  coordinates <- GetTissueCoordinates(object = x, scale = NULL, cols = NULL)
  cells <- cells[cells %in% rownames(x = coordinates)]
  coordinates <- coordinates[cells, ]
  slot(object = x, name = 'coordinates') <- coordinates
  return(x)
}



#' Update pre-V4 Assays generated with SCTransform in the Seurat to the new
#' SCTAssay class
#
#' @param object A Seurat object
#' @export
#' @return A Seurat object with updated SCTAssays
#'
UpdateSCTAssays <- function(object) {
  assays <- Assays(object = object)
  for (assay in assays) {
    if (IsSCT(assay = object[[assay]]) && !inherits(x = object[[assay]], what = "SCTAssay")) {
      object[[assay]] <- as(object =  object[[assay]], Class = "SCTAssay")
    }
  }
  return(object)
}

#%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%
# S4 methods
#%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%

#' @rdname SCTAssay-class
#' @name SCTAssay-class
#'
#' @section Creating an \code{SCTAssay} from an \code{Assay}:
#' Conversion from an \code{Assay} object to an \code{SCTAssay} object by
#' is done by adding the additional slots to the object. If \code{from} has
#' results generated by \code{\link{SCTransform}} from Seurat v3.0.0 to v3.1.1,
#' the conversion will automagically fill the new slots with the data
#'
setAs(
  from = 'Assay',
  to = 'SCTAssay',
  def = function(from) {
    object.list <- sapply(
      X = slotNames(x = from),
      FUN = slot,
      object = from,
      simplify = FALSE,
      USE.NAMES = TRUE
    )
    object.list <- c(
      list('Class' = 'SCTAssay'),
      object.list
    )
    if (IsSCT(assay = from)) {
      vst.slots <- c('vst.set', 'vst.out')
      vst.use <- vst.slots[vst.slots %in% names(x = Misc(object = from))][1]
      vst.res <- Misc(object = from, slot = vst.use)
      umi.assay <- Misc(object = from, slot = "umi.assay")
      if (vst.use == 'vst.out') {
        vst.res <- list(vst.res)
        umi.assay <- list(umi.assay)
      }
      if (length(x = vst.res) == 0) {
        vst.res <- list()
      } else if (length(x = vst.res) > 0) {
        vst.res <- lapply(
          X = 1:length(x = vst.res),
          FUN = function(i) {
            vst.res[[i]]$umi.assay <- umi.assay[[i]]
            return(PrepVSTResults(vst.res = vst.res[[i]], cell.names = colnames(x = from)))
          }
        )
        names(x = vst.res) <- paste0("model", 1:length(x = vst.res))
      }
      if (length(x = vst.res) > 1) {
        vst.res <- merge(x = vst.res[[1]], y = vst.res[2:length(x = vst.res)])
      }
      object.list$misc[[vst.use]] <- NULL
      object.list$SCTModel.list <- vst.res
    }
    return(do.call(what = 'new', args = object.list))
  }
)

setMethod(
  f = 'show',
  signature = 'TransferAnchorSet',
  definition = function(object) {
    cat('An AnchorSet object containing', nrow(x = slot(object = object, name = "anchors")),
        "anchors between the reference and query Seurat objects. \n",
        "This can be used as input to TransferData.")
  }
)

setMethod(
  f = 'show',
  signature = 'IntegrationAnchorSet',
  definition = function(object) {
    cat('An AnchorSet object containing', nrow(x = slot(object = object, name = "anchors")),
        "anchors between", length(x = slot(object = object, name = "object.list")), "Seurat objects \n",
        "This can be used as input to IntegrateData.")
  }
)

setMethod(
  f = 'show',
  signature = 'ModalityWeights',
  definition = function(object) {
    cat(
      'A ModalityWeights object containing modality weights between',
      paste(slot(object = object, name = "modality.assay"), collapse = " and "),
      "assays \n", "This can be used as input to FindMultiModelNeighbors.")
  }
)

setMethod(
  f = 'show',
  signature = 'SCTModel',
  definition = function(object) {
    cat(
      "An sctransform model.\n",
      " Model formula: ", slot(object = object, name = "model"),
      "\n  Parameters stored for", nrow(x = SCTResults(object = object, slot = "feature.attributes")), "features,",
      nrow(x = SCTResults(object = object, slot = "cell.attributes")), "cells")
  }
)

setMethod(
  f = 'show',
  signature = 'SCTAssay',
  definition = function(object) {
    cat('SCTAssay data with', nrow(x = object), 'features for', ncol(x = object),
        'cells, and', length(x = levels(x = object)) , 'SCTModel(s) \n')

    if (length(x = VariableFeatures(object = object)) > 0) {
      top.ten <- head(x = VariableFeatures(object = object), n = 10L)
      top <- 'Top'
      variable <- 'variable'
    } else {
      top.ten <- head(x = rownames(x = object), n = 10L)
      top <- 'First'
      variable <- ''
    }
    features <- paste0(
      variable,
      ' feature',
      if (length(x = top.ten) != 1) {'s'}, ":\n"
    )
    features <- gsub(pattern = '^\\s+', replacement = '', x = features)
    cat(
      top,
      length(x = top.ten),
      features,
      paste(strwrap(x = paste(top.ten, collapse = ', ')), collapse = '\n'),
      '\n'
    )
  }
)

#%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%
# Internal
#%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%

# Internal AddMetaData defintion
#
# @param object An object
# @param metadata A vector, list, or data.frame with metadata to add
# @param col.name A name for meta data if not a named list or data.frame
#
# @return object with metadata added
#
.AddMetaData <- function(object, metadata, col.name = NULL) {
  object <- UpdateSlots(object = object)
  if (is.null(x = col.name) && is.atomic(x = metadata)) {
    stop("'col.name' must be provided for atomic metadata types (eg. vectors)")
  }
  if (inherits(x = metadata, what = c('matrix', 'Matrix'))) {
    metadata <- as.data.frame(x = metadata)
  }
  col.name <- col.name %||% names(x = metadata) %||% colnames(x = metadata)
  if (is.null(x = col.name)) {
    stop("No metadata name provided and could not infer it from metadata object")
  }
  object[[col.name]] <- metadata
  # if (class(x = metadata) == "data.frame") {
  #   for (ii in 1:ncol(x = metadata)) {
  #     object[[colnames(x = metadata)[ii]]] <- metadata[, ii, drop = FALSE]
  #   }
  # } else {
  #   object[[col.name]] <- metadata
  # }
  return(object)
}

# Find the names of collections in an object
#
# @return A vector with the names of slots that are a list
#
Collections <- function(object) {
  collections <- vapply(
    X = slotNames(x = object),
    FUN = function(x) {
      return(any(grepl(pattern = 'list', x = class(x = slot(object = object, name = x)))))
    },
    FUN.VALUE = logical(length = 1L)
  )
  collections <- Filter(f = isTRUE, x = collections)
  return(names(x = collections))
}

# Calculate nCount and nFeature
#
# @param object An Assay object
#
# @return A named list with nCount and nFeature
#
#' @importFrom Matrix colSums
#
CalcN <- function(object) {
  if (IsMatrixEmpty(x = GetAssayData(object = object, slot = "counts"))) {
    return(NULL)
  }
  return(list(
    nCount = colSums(x = object, slot = 'counts'),
    nFeature = colSums(x = GetAssayData(object = object, slot = 'counts') > 0)
  ))
}

# Get the default image of an object
#
# Attempts to find all images associated with the default assay of the object.
# If none present, finds all images present in the object. Returns the name of
# the first image
#
# @param object A Seurat object
#
# @return The name of the default image
#
DefaultImage <- function(object) {
  object <- UpdateSlots(object = object)
  images <- Images(object = object, assay = DefaultAssay(object = object))
  if (length(x = images) < 1) {
    images <- Images(object = object)
  }
  return(images[[1]])
}

# Get the names of objects within a Seurat object that are of a certain class
#
# @param object A Seurat object
# @param classes.keep A vector of names of classes to get
#
# @return A vector with the names of objects within the Seurat object that are of class \code{classes.keep}
#
#' @importFrom stats na.omit
#
FilterObjects <- function(object, classes.keep = c('Assay', 'DimReduc')) {
  object <- UpdateSlots(object = object)
  slots <- na.omit(object = Filter(
    f = function(x) {
      sobj <- slot(object = object, name = x)
      return(is.list(x = sobj) && !is.data.frame(x = sobj) && !is.package_version(x = sobj))
    },
    x = slotNames(x = object)
  ))
  slots <- grep(pattern = 'tools', x = slots, value = TRUE, invert = TRUE)
  slots <- grep(pattern = 'misc', x = slots, value = TRUE, invert = TRUE)
  slots.objects <- unlist(
    x = lapply(
      X = slots,
      FUN = function(x) {
        return(names(x = slot(object = object, name = x)))
      }
    ),
    use.names = FALSE
  )
  object.classes <- sapply(
    X = slots.objects,
    FUN = function(i) {
      return(inherits(x = object[[i]], what = classes.keep))
    }
  )
  object.classes <- which(x = object.classes, useNames = TRUE)
  return(names(x = object.classes))
}

# Find the collection of an object within a Seurat object
#
# @param object A Seurat object
# @param name Name of object to find
#
# @return The collection (slot) of the object
#
FindObject <- function(object, name) {
  collections <- c(
    'assays',
    'graphs',
    'neighbors',
    'reductions',
    'commands',
    'images'
  )
  object.names <- lapply(
    X = collections,
    FUN = function(x) {
      return(names(x = slot(object = object, name = x)))
    }
  )
  names(x = object.names) <- collections
  object.names <- Filter(f = Negate(f = is.null), x = object.names)
  for (i in names(x = object.names)) {
    if (name %in% names(x = slot(object = object, name = i))) {
      return(i)
    }
  }
  return(NULL)
}

# Prepare VST results for use with SCTAssay objects
#
# @param vst.res Results from sctransform::vst
# @param cell.names Vector of valid cell names still in object
#
# @return An SCTModel object.
#
#
PrepVSTResults <- function(vst.res, cell.names) {
  # Prepare cell attribute information
  cell.attrs <- vst.res$cell_attr
  cell.names <- intersect(x = cell.names, y = rownames(x = cell.attrs))
  cell.cols <- c(
    'umi',
    'gene',
    'log_umi',
    'log_gene',
    'umi_per_gene',
    'log_umi_per_gene'
  )
  cell.cols <- intersect(x = cell.cols, y = colnames(x = cell.attrs))
  cell.attrs <- cell.attrs[cell.names, cell.cols, drop = FALSE]
  colnames(x = cell.attrs) <- gsub(
    pattern = 'gene',
    replacement = 'feature',
    x = colnames(x = cell.attrs)
  )
  if (!is.null(x = vst.res$cells_step1)) {
    cell.attrs[, "cells_step1"] <- FALSE
    cells_step1 <- intersect(x = vst.res$cells_step1,
                             y = rownames(x = cell.attrs))
    cell.attrs[cells_step1, "cells_step1"] <- TRUE
  }
  # Prepare feature attribute information
  feature.attrs <- vst.res$gene_attr
  feature.cols <- c(
    'detection_rate',
    'gmean',
    'variance',
    'residual_mean',
    'residual_variance'
  )
  feature.cols <- intersect(x = feature.cols, y = colnames(x = feature.attrs))
  feature.attrs <- feature.attrs[, feature.cols, drop = FALSE]
  feature.attrs <- cbind(feature.attrs, vst.res$model_pars_fit[rownames(feature.attrs), , drop = FALSE])

  if (!is.null(x = vst.res$genes_log_gmean_step1)) {
    feature.attrs[,"genes_log_gmean_step1"] <- FALSE
    genes_step1 <- intersect(
      x = names(vst.res$genes_log_gmean_step1),
      y = rownames(feature.attrs)
    )
    feature.attrs[genes_step1,"genes_log_gmean_step1"] <- TRUE
  }
  # Prepare clipping information
  clips <- list(
    'vst' = vst.res$arguments$res_clip_range,
    'sct' = vst.res$arguments$sct.clip.range
  )
  vst.res.SCTModel  <- SCTModel(
    feature.attributes = feature.attrs,
    cell.attributes = cell.attrs,
    clips = clips,
    umi.assay = vst.res$umi.assay %||% "RNA",
    model =  vst.res$model_str,
    arguments =  vst.res$arguments
  )
  return(vst.res.SCTModel)
}

# Return a null image
#
# @param mode Image representation to return
# see \code{\link{GetImage}} for more details
#
#' @importFrom grid nullGrob
#' @importFrom grDevices as.raster
#
NullImage <- function(mode) {
  image <- switch(
    EXPR = mode,
    'grob' = nullGrob(),
    'raster' = as.raster(x = new(Class = 'matrix')),
    'plotly' = list('visible' = FALSE),
    'raw' = NULL,
    stop("Unknown image mode: ", mode, call. = FALSE)
  )
  return(image)
}

# Check to see if projected loadings have been set
#
# @param object a DimReduc object
#
# @return TRUE if proejcted loadings have been set, else FALSE
#
Projected <- function(object) {
  projected.dims <- dim(x = slot(object = object, name = 'feature.loadings.projected'))
  if (all(projected.dims == 1)) {
    return(!all(is.na(x = slot(object = object, name = 'feature.loadings.projected'))))
  }
  return(!all(projected.dims == 0))
}

# Subset cells in vst data
# @param sct.info A vst.out list
# @param cells vector of cells to retain
# @param features vector of features to retain
SubsetVST <- function(sct.info, cells, features) {
  cells.keep <- intersect(x = cells, y = rownames(x = sct.info$cell_attr))
  sct.info$cell_attr <- sct.info$cell_attr[cells.keep, ]
  # find which subset of features are in the SCT assay
  feat.keep <- intersect(x = features, y = rownames(x = sct.info$gene_attr))
  sct.info$gene_attr <- sct.info$gene_attr[feat.keep, ]
  return(sct.info)
}

# Get the top
#
# @param data Data to pull the top from
# @param num Pull top \code{num}
# @param balanced Pull even amounts of from positive and negative values
#
# @return The top \code{num}
# @seealso \{code{\link{TopCells}}} \{code{\link{TopFeatures}}}
#
Top <- function(data, num, balanced) {
  nr <- nrow(x = data)
  if (num > nr) {
    warning("Requested number is larger than the number of available items (",
            nr, "). Setting to ", nr , ".", call. = FALSE)
    num <- nr
  }
  if (num == 1) {
    balanced <- FALSE
  }
  top <- if (balanced) {
    num <- round(x = num / 2)
    data <- data[order(data, decreasing = TRUE), , drop = FALSE]
    positive <- head(x = rownames(x = data), n = num)
    negative <- rev(x = tail(x = rownames(x = data), n = num))

    # remove duplicates
    if (positive[num] == negative[num]) {
      negative <- negative[-num]
    }
    list(positive = positive, negative = negative)
  } else {
    data <- data[rev(x = order(abs(x = data))), , drop = FALSE]
    top <- head(x = rownames(x = data), n = num)
    top[order(data[top, ])]
  }
  return(top)
}

# Update Seurat assay
#
# @param old.assay Seurat2 assay
# @param assay Name to store for assay in new object
#
UpdateAssay <- function(old.assay, assay){
  cells <- colnames(x = old.assay@data)
  counts <- old.assay@raw.data
  data <- old.assay@data
  if (!inherits(x = counts, what = 'dgCMatrix')) {
    counts <- as(object = as.matrix(x = counts), Class = 'dgCMatrix')
  }
  if (!inherits(x = data, what = 'dgCMatrix')) {
    data <- as(object = as.matrix(x = data), Class = 'dgCMatrix')
  }
  new.assay <- new(
    Class = 'Assay',
    counts = counts[, cells],
    data = data,
    scale.data = old.assay@scale.data %||% new(Class = 'matrix'),
    meta.features = data.frame(row.names = rownames(x = counts)),
    var.features = old.assay@var.genes,
    key = paste0(assay, "_")
  )
  return(new.assay)
}

# Update dimension reduction
#
# @param old.dr Seurat2 dimension reduction slot
# @param assay.used Name of assay used to compute dimension reduction
#
UpdateDimReduction <- function(old.dr, assay) {
  new.dr <- list()
  for (i in names(x = old.dr)) {
    cell.embeddings <- old.dr[[i]]@cell.embeddings %||% new(Class = 'matrix')
    feature.loadings <- old.dr[[i]]@gene.loadings %||% new(Class = 'matrix')
    stdev <- old.dr[[i]]@sdev %||% numeric()
    misc <- old.dr[[i]]@misc %||% list()
    new.jackstraw <- UpdateJackstraw(old.jackstraw = old.dr[[i]]@jackstraw)
    old.key <- old.dr[[i]]@key
    if (length(x = old.key) == 0) {
      old.key <- gsub(pattern = "(.+?)(([0-9]+).*)", replacement = "\\1",  x = colnames(cell.embeddings)[[1]])
      if (length(x = old.key) == 0) {
        old.key <- i
      }
    }
    new.key <- suppressWarnings(expr = UpdateKey(key = old.key))
    colnames(x = cell.embeddings) <- gsub(
      pattern = old.key,
      replacement = new.key,
      x = colnames(x = cell.embeddings)
    )
    colnames(x = feature.loadings) <- gsub(
      pattern = old.key,
      replacement = new.key,
      x = colnames(x = feature.loadings)
    )
    new.dr[[i]] <- new(
      Class = 'DimReduc',
      cell.embeddings = as(object = cell.embeddings, Class = 'matrix'),
      feature.loadings = as(object = feature.loadings, Class = 'matrix'),
      assay.used = assay,
      stdev = as(object = stdev, Class = 'numeric'),
      key = as(object = new.key, Class = 'character'),
      jackstraw = new.jackstraw,
      misc = as(object = misc, Class = 'list')
    )
  }
  return(new.dr)
}

# Update jackstraw
#
# @param old.jackstraw
#
UpdateJackstraw <- function(old.jackstraw) {
  if (is.null(x = old.jackstraw)) {
    new.jackstraw <- new(
      Class = 'JackStrawData',
      empirical.p.values = new(Class = 'matrix'),
      fake.reduction.scores = new(Class = 'matrix'),
      empirical.p.values.full = new(Class = 'matrix'),
      overall.p.values = new(Class = 'matrix')
    )
  } else {
    if (.hasSlot(object = old.jackstraw, name = 'overall.p.values')) {
      overall.p <- old.jackstraw@overall.p.values %||% new(Class = 'matrix')
    } else {
      overall.p <- new(Class = 'matrix')
    }
    new.jackstraw <- new(
      Class = 'JackStrawData',
      empirical.p.values = old.jackstraw@emperical.p.value %||% new(Class = 'matrix'),
      fake.reduction.scores = old.jackstraw@fake.pc.scores %||% new(Class = 'matrix'),
      empirical.p.values.full = old.jackstraw@emperical.p.value.full %||% new(Class = 'matrix'),
      overall.p.values = overall.p
    )
  }
  return(new.jackstraw)
}

# Update a Key
#
# @param key A character to become a Seurat Key
#
# @return An updated Key that's valid for Seurat
#
UpdateKey <- function(key) {
  if (grepl(pattern = '^[[:alnum:]]+_$', x = key)) {
    return(key)
  } else {
    new.key <- regmatches(
      x = key,
      m = gregexpr(pattern = '[[:alnum:]]+', text = key)
    )
    new.key <- paste0(paste(unlist(x = new.key), collapse = ''), '_')
    if (new.key == '_') {
      new.key <- paste0(RandomName(length = 3), '_')
    }
    warning(
      "Keys should be one or more alphanumeric characters followed by an underscore, setting key from ",
      key,
      " to ",
      new.key,
      call. = FALSE,
      immediate. = TRUE
    )
    return(new.key)
  }
}

# Update slots in an object
#
# @param object An object to update
#
# @return \code{object} with the latest slot definitions
#
UpdateSlots <- function(object) {
  object.list <- sapply(
    X = slotNames(x = object),
    FUN = function(x) {
      return(tryCatch(
        expr = slot(object = object, name = x),
        error = function(...) {
          return(NULL)
        }
      ))
    },
    simplify = FALSE,
    USE.NAMES = TRUE
  )
  object.list <- Filter(f = Negate(f = is.null), x = object.list)
  object.list <- c('Class' = class(x = object)[1], object.list)
  object <- do.call(what = 'new', args = object.list)
  for (x in setdiff(x = slotNames(x = object), y = names(x = object.list))) {
    xobj <- slot(object = object, name = x)
    if (is.vector(x = xobj) && !is.list(x = xobj) && length(x = xobj) == 0) {
      slot(object = object, name = x) <- vector(mode = class(x = xobj), length = 1L)
    }
  }
  return(object)
}

# Pulls the proper data matrix for merging assay data. If the slot is empty, will return an empty
# matrix with the proper dimensions from one of the remaining data slots.
#
# @param assay Assay to pull data from
# @param slot Slot to pull from
#
# @return Returns the data matrix if present (i.e.) not 0x0. Otherwise, returns an
# appropriately sized empty sparse matrix
#
ValidateDataForMerge <- function(assay, slot) {
  mat <- GetAssayData(object = assay, slot = slot)
  if (any(dim(x = mat) == c(0, 0))) {
    slots.to.check <- setdiff(x = c("counts", "data", "scale.data"), y = slot)
    for (ss in slots.to.check) {
      data.dims <- dim(x = GetAssayData(object = assay, slot = ss))
      data.slot <- ss
      if (!any(data.dims == c(0, 0))) {
        break
      }
    }
    if (any(data.dims == c(0, 0))) {
      stop("The counts, data, and scale.data slots are all empty for the provided assay.")
    }
    mat <- Matrix(
      data = 0,
      nrow = data.dims[1],
      ncol = data.dims[2],
      dimnames = dimnames(x = GetAssayData(object = assay, slot = data.slot))
    )
    mat <- as(object = mat, Class = "dgCMatrix")
  }
  return(mat)
}